Microtubule Function and Cell Division

CELL AND DEVELOPMENTAL BIOLOGY

GROUP LEADER:
Isabelle Vernos (ICREA Research Professor and member of the ERC Scientific Council)

POSTDOCTORAL FELLOWS:
Mónica Rodríguez, Georgina Garrido, Álvaro Aranguren, Claudia Conte

PhD STUDENTS:
Miquel Rosas, Krystal Timón, Farners Amargant, Alejandra Laguillo, Aitor Modol, Ivan Zadra (since April)

TECHNICIANS:
Nuria Mallol, Leonor Ávila

Summary

The development and growth of multicellular organisms as well as the renewal and homeostasis of their tissues rely on the controlled proliferation of their cells. Errors during cell division are deleterious for a cell and an organism as they can generate aneuploidies, a hallmark of particularly aggressive tumours and one of the main causes of spontaneous abortions.

Cell division entails a dramatic reorganization of most cellular components and the assembly of the bipolar spindle, a microtubule (MT) based apparatus that provides the forces and mechanical support for moving and segregating the chromosomes accurately. Most animal cells enter mitosis with duplicated centrosomes that provide an active source of dynamic MTs but spindle assembly relies largely on the nucleation of acentrosomal MTs occurring in a RanGTP dependent manner around the chromosomes after nuclear envelope breakdown. During the last year, we have identified and characterized KBP as a binding partner of the kinesin-like protein Hklp2/Kif15. In collaboration with the group of Joan Roig (CSIC-IRB) we identified a phosphorylation dependent mechanism by which the nuclear protein TPX2 associates with the centrosome before nuclear envelope breakdown to participate in centrosome separation.

The kinesin-like protein Hklp2/Kif15 localizes to the spindle microtubules. In cells silenced for its binding partner KBP, it fails to accumulate in the spindle mid-zone (see Brouwers et al, 2017).

Fig. 1

The kinesin-like protein Hklp2/Kif15 localizes to the spindle microtubules. In cells silenced for its binding partner KBP, it fails to accumulate in the spindle mid-zone (see Brouwers et al, 2017).

Research Projects

  • Understanding the regulation of microtubule minus-end dynamics during mitosis (Alejandra Laguillo, Claudia Conte)
  • Role of microtubule polyglutamylation during mitosis (Monica Rodriguez, Ivan Zadra)
  • Identification and functional characterization of the RanGTP microtubule proteome and novel SAFs (Spindle Assembly Factors) regulated by RanGTP (Miquel Rosas, Tommaso Cavazza)
  • Spatial and temporal control of microtubule assembly during mitosis and its role in spindle assembly and chromosome segregation (Krystal Timon)
  • The role of the sperm centrosome in fertility (Farners Amargant in collaboration with Clinica EUGIN))
  • Identification of the TPX2 and Aurora A interactomes in mitotic cells (Georgina Garrido, Alvaro Aranguren)

Selected Publications

Eibes S, Gallisà-Suñé N, Rosas-Salvans M, Martínez-Delgado P, Vernos I, Roig J.
“Nek9 Phosphorylation Defines a New Role for TPX2 in Eg5-Dependent Centrosome Separation before Nuclear Envelope Breakdown.”
Curr Biol, 8;28(1):121-129.e4. Epub 2017 Dec 21.

Brouwers N, Mallol Martinez N, Vernos I.
“Role of Kif15 and its novel mitotic partner KBP in K-fiber dynamics and chromosome alignment.”
PLoS One, 12(4):e0174819 (2017).